Antipsychotics

Question 1

Describe the dopamine theory of Schizophrenia

Answer 1

• amphetamines (which upregulate dopamine) produce symptoms indistinguishable from Schizophrenia
• D2-receptor agonists produce similar symptoms in animals and exacerbate symptoms in humans
• increased dopamine content in amygdala in brains of Schizophrenics
• increased dopamine synthesis and release in brains of Schizophrenics

Question 2

Describe the glutamate theory of Schizophrenia

Answer 2

• NMDA receptor antagonists produce psychotic symptoms
• decreased glutamate and receptor density in Schizphrenic brains
• transgenic mice with decreased NMDA receptor expression show stereotypic Schizophrenic behaviour and decreased social interaction (and respond to treatment with anti-psychotics)

Question 3

What distinguishes 1st gen (typical) and 2nd gen (atypical) antipsychotics?

Answer 3

• receptor profile
• incidence of extra-pyramidal side effects (less in 2nd gen)
• efficacy in treatment resistant patients (better in 2nd gen) - clozapine is drug of choice
• efficacy against negative symptoms (better in 2nd gen)

Question 4

What are the behavioural side effects of antipsychotics?

Answer 4

• apathy and few emotions
• drowsy
• decreased initiative
• aggressive tendencies inhibited

Question 5

What are the possible motor side effects if antipsychotics?

Answer 5

• acute and reversible Parkinson-like symptoms (due to block in nigrostriatal dopamine receptors)
• slow developing tardive dyskinesia (irreversible) - involuntary movement of the face due to increased dopamine receptors in the corpus striatum

Question 6

Name some unwanted effects of antipsychotics

Answer 6

• endocrine: increased prolactin secretion
• anti-muscarinic: blurred vision, dry eyes/mouth, constipation
• a-adrenoreceptor: orthostatic hypotension
• H1-blocking: sedative and anti-emetic
• neuroleptic malignant syndrome
• jaundice
• leukopenia and agranulocytosis
• diabetes
• skin reactions

Question 7

What are the common receptor specificities for 1st and 2nd gen antipsychotics and their side effects?

Answer 7

1st gen:

• receptor: D1, D2, H1, 5-HT2A
• side effects: sedative, weight gain, extra-pyramidal, increased prolactin

2nd gen:

• receptor: D2, a1, H1, 5-HT2A
• side effects: sedation, weight gain, diabetes, hypotension